Disease relevance of M6PR

• A recombinant baculovirus containing the cDNA for the full-length bovine cation-dependent mannose 6-phosphate receptor (CD-MPR) was generated by homologous recombination [1].

High impact information on M6PR

• Translation of CD Man-6-P receptor mRNA in Xenopus laevis oocytes results in a protein that binds specifically to phosphomannan-Sepharose, thus demonstrating that our cDNA clones encode a functional receptor [2].
• These findings indicate that the cytoplasmic tail of the CD-MPR contains a signal that prevents the receptor from trafficking to lysosomes [3].
• Antibodies that recognize the cytoplasmic domain of either the CI-MPR or the CD-MPR routinely give membrane preparations that are approximately 50-fold enriched in each of the respective receptors, as determined by quantitative Western blotting [4].
• The 46-kDa mannose 6-phosphate receptor contains multiple binding sites for clathrin adaptors [5].
• Coated vesicle adaptors of the trans-Golgi network displayed poor binding to LAP, but high affinity binding to the cytoplasmic tail of the 46-kDa mannose 6-phosphate receptor, which is included in clathrin-coated pits of the trans-Golgi network [6].

Biological context of M6PR

• The structural requirements for oligomerization and the generation of a functional mannose 6-phosphate (Man-6-P) binding site of the cation-dependent mannose 6-phosphate receptor (CD-MPR) were analyzed [7].
• We have studied the expression of the IGF-II/M6P receptor in fetal bovine tissues from 5 through 36 weeks' gestation [8].
• The bovine cation-dependent mannose 6-phosphate receptor (CD-MPR) contains five potential N-linked glycosylation sites, four of which are utilized [9].

Anatomical context of M6PR

• Ligand blot analysis using bovine testes beta-galactosidase showed that the monomeric form of the CD-MPR from bovine liver and testes is capable of binding Man-6-P [7].
• Chemical cross-linking studies on affinity-purified CD-MPR and on solubilized membranes containing the receptor indicate that the CD-MPR exists as a homodimer [7].
• We have developed a method for the isolation of the subcellular organelles from bovine liver which are enriched in the cation-independent mannose 6-phosphate receptor (CI-MPR) and the cation-dependent mannose 6-phosphate receptor (CD-MPR) [4].
• Immunostaining of the tissues showed that both receptors localize to hepatocytes at all the ages and, additionally, the CD-MPR was reactive in megakaryocytes at early stages [10].
• CI-MPR expression decreases progressively from 18-day fetuses to adults, whereas the CD-MPR showed a transient decrease in newborn and at the 5th day after birth [10].

Associations of M6PR with chemical compounds

• A series of chemically synthesized oligomannosides that contain mannose 6-phosphate residues were utilized as inhibitors of the binding of beta-galactosidase to high (CI-MPR, 215 kDa) and low (CD-MPR, 41-46 kDa) molecular mass mannose 6-phosphate receptor from bovine testes in order to probe the specificity of each receptor [11].
• Mammalian tissues express both cation-dependent (CD-MPR) and cation-independent (CI-MPR) mannose-6-phosphate receptors, which mediate the targeting of acid hydrolases to lysosomes [10].

Physical interactions of M6PR

• Although the receptors exhibited similar relative specificities for phosphomonoesters, phosphodiesters did not inhibit binding of ligand to CD-MPR and only weakly inhibited binding to CI-MPR [11].

Other interactions of M6PR

• In analogy, the binding of [125I]IGF-II to bovine adrenal membranes was characteristic of the IGF-II/M6P receptor and no differences between cortical and medullary membrane fractions were found [12].
• In both regions of the bovine adrenal gland the IGF-II/M6P receptor is much more abundant than the IGF-I receptor [12].

Analytical, diagnostic and therapeutic context of M6PR

• We have analyzed this interaction between the Golgi-restricted AP1 complex and the plasma membrane-restricted AP2 complex with the MPR46 tail in vitro by using a biosensor [5].
• Chicken IgY antibodies specifically recognized the human and bovine 270-kDa M6P/IGFII-R but not the 46-kDa M6P-R, as documented by immunoprecipitation and immunobloting [13].
• Immunoblotting was performed with anti-bovine IGF-II/M6P receptor antiserum [8].
• To evaluate the function of these oligosaccharides, site-directed mutagenesis was used to generate glycosylation-deficient CD-MPR mutants lacking various potential glycosylation sites [9].
• In conclusion, the full-length CD-MPR produced in P. pastoris is structurally and functionally suitable for crystallization studies [14].

References